Some Drugs Have Two Faces: Paradoxical Colitis in a Patient with Psoriatic Arthritis Previously Treated with Etanercept and IL-17 Inhibitors.

Tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) inhibitors are among the most potent treatments for inflammatory arthropathies including rheumatoid arthritis, psoriasis, and spondyloarthropathies. The availability of these biologic agents have revolutionized the management of these conditions and improved patient outcomes. Though generally safe, these biologics may contribute to the induction or exacerbation of colitis. This paradoxical colitis has been observed in patients on TNF-α inhibitor etanercept and IL-17 inhibitors (secukinumab and ixekizumab). We report a case of a 46-year-old female with psoriasis and psoriatic arthritis who presented with gastrointestinal symptoms after treatment with etanercept and IL-17 inhibitors. She was later diagnosed with paradoxical indeterminate colitis that was masked and treated by subsequent biologics given for her RA and psoriatic arthritis. In this report, we will discuss the importance of considering paradoxical colitis in the differential diagnosis for patients even several years after TNF-α/IL-17 inhibitor initiation and explain why careful consideration must be made when initiating these colitis-inducing agents to treat patients with inflammatory disorders.

Photorearrangement of [8]-2,6-Pyridinophane N-Oxide.

Reaction pathways operative when pyridinophane N-oxides are photoirradiated have been studied using time course analyses and careful isolation of photolabile intermediates with support from DFT calculations. Based on the data and the isolation of two previously unknown heterocyclophanes, we outline a unified mechanistic scheme that explains competing processes under varying photochemical conditions.

Expanded Helicenes as Synthons for Chiral Macrocyclic Nanocarbons.

Expanded helicenes are large, structurally flexible π-frameworks that can be viewed as building blocks for more complex chiral nanocarbons. Here we report a gram-scale synthesis of an alkyne-functionalized expanded [11]helicene and its single-step transformation into two structurally and functionally distinct types of macrocyclic derivatives: (1) a figure-eight dimer via alkyne metathesis (also gram scale) and (2) two arylene-bridged expanded helicenes via Zr-mediated, formal [2+2+n] cycloadditions. The phenylene-bridged helicene displays a substantially higher enantiomerization barrier (22.1 kcal/mol) than its helicene precursor (<11.9 kcal/mol), which makes this a promising strategy to access configurationally stable expanded helicenes. In contrast, the topologically distinct figure-eight retains the configurational lability of the helicene precursor. Despite its lability in solution, this compound forms homochiral single crystals. Here, the configuration is stabilized by an intricate network of two distinct yet interconnected helical superstructures. The enantiomerization mechanisms for all new compounds were probed using density functional theory, providing insight into the flexibility of the figure-eight and guidance for future synthetic modifications in pursuit of non-racemic macrocycles.

Fjord-Edge Graphene Nanoribbons with Site-Specific Nitrogen Substitution.

The synthesis of graphene nanoribbons (GNRs) that contain site-specifically substituted backbone heteroatoms is one of the essential goals that must be achieved in order to control the electronic properties of these next generation organic materials. We have exploited our recently reported solid-state topochemical polymerization/cyclization-aromatization strategy to convert the simple 1,4-bis(3-pyridyl)butadiynes 3a,b into the fjord-edge nitrogen-doped graphene nanoribbon structures 1a,b (fjord-edge N2[8]GNRs). Structural assignments are confirmed by CP/MAS 13C NMR, Raman, and XPS spectroscopy. The fjord-edge N2[8]GNRs 1a,b are promising precursors for the novel backbone nitrogen-substituted N2[8]AGNRs 2a,b. Geometry and band calculations on N2[8]AGNR 2c indicate that this class of nanoribbons should have unusual bonding topology and metallicity.

Solid-State Order and Charge Mobility in [5]- to [12]Cycloparaphenylenes.

We report a computational study of mesoscale morphology and charge-transport properties of radially π-conjugated cycloparaphenylenes ([ n]CPPs) of various ring sizes ( n = 5-12, where n is the number of repeating phenyl units). These molecules are considered structural constituents of fullerenes and carbon nanotubes. [ n]CPP molecules are nested in a unique fashion in the solid state. Molecular dynamics simulations show that while intramolecular structural stability (order) increases with system size, intermolecular structural stability decreases. Density functional calculations reveal that reorganization energy, an important parameter in charge transfer, decreases as n is increased. Intermolecular charge-transfer electronic couplings in the solid state are relatively weak (due to curved π-conjugation and loose intermolecular contacts) and are on the same order of magnitude (∼10 meV) for each system. Intrinsic charge-carrier mobilities were simulated from kinetic Monte Carlo simulations; hole mobilities increased with system size and scaled as ∼ n4. We predict that disordered [ n]CPPs exhibit hole mobilities as high as 2 cm2/(V·s). Our computations show a strong correlation between reorganization energy and hole mobility (µ ∼ λ-4). Quantum mechanical calculations were performed on cofacially stacked molecular pairs for varying phenyl units and reveal that orbital delocalization is responsible for both decreasing reorganization energies and electronic couplings as n is increased.

Impact of morphology, side-chains, and crystallinity on charge-transport properties of π-extended double helicenes.

We report a computational study on the effect of side-chain substitution, heteroaromatic substitution and unique crystal packing on the charge transport and mobility of three double helicene molecules. These double helicene (DH) molecules, having curved π-conjugation, are structural hybrids of non-planar [6]helicene and planar tribenzo[b,n,pqr]perylene (TBP). We find that side-chain substitution has only a effect on intrinsic electronic properties in DHs but dramatically impacts the packing arrangement, morphologies and transport network, exhibited in calculated charge transport parameters. Interestingly, the dimensionality of the transport evolves from one dimensional to three dimensional with side-chain substitution (DH2) and heteroaromatic substitution (DH3). Using two different well-known transport models, we have established a direct link between the morphology, transport connectivity, and hole mobilities. While both unsubstituted and substituted DHs exhibit high hole mobilities in the ordered phase, the results show that with inclusion of positional disorder, the mobilities of disordered DH1 and DH3 are lower while the mobility of DH2 remain nearly unchanged. We relate this effect to the dimensionality of their unique transport networks. These DH molecules are promising organic semiconductors with high mobilities in ordered and disordered phases, with predicted values that lie in the range of ∼1 to 10 cm2 V-1 s-1.

Conjugated Trimeric Scaffolds Accessible from Indolyne Cyclotrimerizations: Synthesis, Structures, and Electronic Properties.

We report the design and synthesis of a new class of indole-based conjugated trimers. The targeted compounds are accessed from in situ generated, highly reactive indolyne intermediates using Pd-catalyzed cyclotrimerization reactions. By harnessing three indolyne isomers, six isomeric indole trimers are accessible, none of which have been previously synthesized. Using computational analysis, we describe the structural and photophysical properties of these unique compounds. This study showcases the use of indolynes in transition metal-catalyzed reactions, while providing access to a new class of conjugated trimers, including highly bent heteroaromatic compounds. Computations indicate that, despite differences in planarity between the molecules, the photophysical properties of each trimer are derived from the N-methylindole building block. Excited state behavior follows predicable patterns.

Synthesis of N = 8 Armchair Graphene Nanoribbons from Four Distinct Polydiacetylenes.

We demonstrate a highly efficient thermal conversion of four differently substituted polydiacetylenes (PDAs 1 and 2a-c) into virtually indistinguishable N = 8 armchair graphene nanoribbons ([8]AGNR). PDAs 1 and 2a-c are themselves easily accessed through photochemically initiated topochemical polymerization of diynes 3 and 4a-c in the crystal. The clean, quantitative transformation of PDAs 1 and 2a-c into [8]AGNR occurs via a series of Hopf pericyclic reactions, followed by aromatization reactions of the annulated polycyclic aromatic intermediates, as well as homolytic bond fragmentation of the edge functional groups upon heating up to 600 °C under an inert atmosphere. We characterize the different steps of both processes using complementary spectroscopic techniques (CP/MAS 13C NMR, Raman, FT-IR, and XPS) and high-resolution transmission electron microscopy (HRTEM). This novel approach to GNRs exploits the power of crystal engineering and solid-state reactions by targeting very large organic structures through programmed chemical transformations. It also affords the first reported [8]AGNR, which can now be synthesized on a large scale via two operationally simple and discrete solid-state processes.

Pica during pregnancy among Mexican-born women: a formative study.

Although pica, the craving and purposive consumption of non-food substances, is common among many populations, especially during pregnancy, the health consequences are not well understood. Further, very little is known about pica among Mexican populations in the United States and Mexico. Therefore, we conducted formative research to understand pica in this understudied population. Our objectives were to identify the frequency and types of pica behaviours, to understand perceived aetiologies and consequences of pica and to ascertain if the behaviour was common enough to warrant a larger study. We held nine focus group discussions (three in the Salinas Valley, California; six in Xoxocotla, Morelos, Mexico) with 76 Mexican-born women who were currently pregnant or had delivered within the past 2 years. Earth, adobe, bean stones and ice were the most commonly reported pica substances. Twenty-eight of the 76 participants (37%) reported ever engaging in pica; 22 participants (29%) reported doing so during pregnancy. The proportion of women reporting pica in the United States and Mexico was 43% and 34%, respectively. Women attributed pica to the overwhelming organoleptic appeal of pica substances (especially smell and texture) and to micronutrient deficiencies. Perceived consequences of unfulfilled pica cravings were birthmarks or fetal loss; fulfilled pica cravings were also thought to be generally harmful to the mother or child, with several women specifying toxic lead, pesticides or 'worms'. In sum, pica among Mexican women is common enough to warrant a larger epidemiologic study of its sociodemographic correlates and physiological consequences.

Economic Costs of Diabetes in the U.S. in 2022.

OBJECTIVE: This study updates previous estimates of the economic burden of diagnosed diabetes, with calculation of the health resource use and indirect costs attributable to diabetes in 2022. RESEARCH DESIGN AND METHODS: We combine the demographics of the U.S. population in 2022 with diabetes prevalence, from national survey data, epidemiological data, health care cost data, and economic data, into a Cost of Diabetes Economic Model to estimate the economic burden at the population and per capita levels. Health resource use and associated medical costs are analyzed by age, sex, race/ethnicity, comorbid condition, and health service category. Data sources include national surveys (2015-2020 or most recent available), Medicare standard analytic files (2020), and administrative claims data from 2018 to 2021 for a large commercially insured population in the U.S. RESULTS: The total estimated cost of diagnosed diabetes in the U.S. in 2022 is $412.9 billion, including $306.6 billion in direct medical costs and $106.3 billion in indirect costs attributable to diabetes. For cost categories analyzed, care for people diagnosed with diabetes accounts for 1 in 4 health care dollars in the U.S., 61% of which are attributable to diabetes. On average people with diabetes incur annual medical expenditures of $19,736, of which approximately $12,022 is attributable to diabetes. People diagnosed with diabetes, on average, have medical expenditures 2.6 times higher than what would be expected without diabetes. Glucose-lowering medications and diabetes supplies account for ∼17% of the total direct medical costs attributable to diabetes. Major contributors to indirect costs are reduced employment due to disability ($28.3 billion), presenteeism ($35.8 billion), and lost productivity due to 338,526 premature deaths ($32.4 billion). CONCLUSIONS: The inflation-adjusted direct medical costs of diabetes are estimated to rise 7% from 2017 and 35% from 2012 calculations (stated in 2022 dollars). Following decades of steadily increasing prevalence of diabetes, the overall estimated prevalence in 2022 remains relatively stable in comparison to 2017. However, the absolute number of people with diabetes has grown and contributes to increased health care expenditures, particularly per capita spending on inpatient hospital stays and prescription medications. The enormous economic toll of diabetes continues to burden society through direct medical and indirect costs.

Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus.

Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.

Stability assessment of gas mixtures containing monoterpenes in varying cylinder materials and treatments.

Studies of climate change increasingly recognize the diverse influences exerted by monoterpenes in the atmosphere, including roles in particulates, ozone formation, and oxidizing potential. Measurements of key monoterpenes suggest atmospheric mole fractions ranging from low pmol/mol (parts-per-trillion; ppt) to nmol/mol (parts-per-billion; ppb), depending on location and compound. To accurately establish the mole fraction trends, assess the role of monoterpenes in atmospheric chemistry, and relate measurement records from many laboratories and researchers, it is essential to have good calibration standards. The feasibility of preparing well-characterized, stable gas cylinder standards for monoterpenes at the nmol/mol level was previously tested using treated (Aculife IV) aluminum gas cylinders at NIST. Results for 4 of the 11 monoterpenes, monitored versus an internal standard of benzene, indicated stability in these treated aluminum gas cylinders for over 6 months and projected long-term (years) stability. However, the mole fraction of the key monoterpene ß-pinene decreased, while the mole fractions of α-pinene, d-limonene (R-(+)-limonene), p-cymene, and camphene (a terpene not present in the initial gas mixture) increased, indicating a chemical transformation of ß-pinene to these species. A similar pattern of decreasing mole fraction was observed in α-pinene where growth of d-limonene, p-cymene, and camphene has been observed in treated gas cylinders prepared with a mixture of just α-pinene and benzene as the internal standard. The current research discusses the testing of other cylinders and treatments for the potential of long-term stability of monoterpenes in a gas mixture. In this current study, a similar pattern of decreasing mole fraction, although somewhat improved short-term stability, was observed for ß-pinene and α-pinene, with growth of d-limonene, p-cymene, and camphene, in nickel-plated carbon steel cylinders. ß-Pinene and α-pinene showed excellent stability at over 6 months in aluminum cylinders treated with a different process (Experis) than used in the original study.

Subthalamic discharges as a causal determinant of parkinsonian motor deficits.

OBJECTIVE: We have reported that intrinsic membrane properties, especially T-type Ca2+ channels, play a key role in the genesis of burst discharges in the subthalamic nucleus (STN) and parkinsonian locomotor symptoms. Whether deep brain stimulation (DBS) exerts its clinical benefits on Parkinson disease (PD) with changes in T currents or other conductances, however, remains elusive. METHODS: Different stimulation protocols, including constant currents of opposite polarity, were applied to STN in vivo or in vitro, and the electrophysiological and behavioral effects were documented in normal and parkinsonian rodents. The effect of correlatively adjusted DBS protocols was also explored in 3 PD patients. RESULTS: Delivery of negative constant current into STN dramatically ameliorated locomotor deficits in parkinsonian rats. It also depolarized STN neurons and decreased T-channel availability as well as burst discharges. In contrast, delivery of positive constant currents to STN induced PD-like locomotor deficits and increased STN burst discharges in normal rats. In addition, the therapeutic effect of DBS was greatly improved in 3 PD patients simply by increasing the pulse width from 60 to 240 microseconds, even at a lower stimulation frequency of 60 Hz. INTERPRETATION: The increased tendency of STN burst discharges may by itself serve as a direct cause of parkinsonian locomotor deficits, even in the absence of deranged dopaminergic innervation. Effective DBS therapy in PD very likely relies on adequate depolarization, and consequent modification of the relevant ionic currents and discharge patterns, of STN neurons.

Incidence of Interstitial Lung Disease in Patients With Rheumatoid Arthritis Treated With Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs.

Importance: Current data are lacking regarding the risk of biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use on the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Objective: To determine the risk of developing ILD in patients with RA undergoing treatment with different b/tsDMARDs. Design, Setting, and Participants: Retrospective cohort study using claims data from the Optum Clinformatics Data Mart between December 2003 and December 2019. Adult patients with RA, 1 year or more of continuous enrollment, treatment with a b/tsDMARD of interest, and without preexisting ILD were included. Data were analyzed from October 2021 to April 2022. Exposures: New administration of adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib. Main Outcomes and Measures: Crude incidence rates (IRs) for the development of ILD were calculated. The risk of ILD across different b/tsDMARDs was compared using Cox-regression models. A sensitivity analysis using a prevalent new-user cohort design compared patients treated with tofacitinib and adalimumab. Results: A total of 28 559 patients with RA (mean [SD] age 55.6 [13.7] years; 22 158 female [78%]) were treated with adalimumab (13 326 patients), abatacept (5676 patients), rituximab (5444 patients), tocilizumab (2548 patients), or tofacitinib (1565 patients). Crude IRs per 1000 person-years for ILD were 3.43 (95% CI 2.85-4.09) for adalimumab, 4.46 (95% CI 3.44-5.70) for abatacept, 6.15 (95% CI 4.76-7.84) for rituximab, 5.05 (95% CI 3.47-7.12) for tocilizumab, and 1.47 (95% CI 0.54-3.27) for tofacitinib. After multiple adjustments, compared with patients treated with adalimumab, patients treated with tofacitinib had a lower risk of ILD (adjusted hazard ratio [aHR] 0.31; 95% CI, 0.12-0.78; P = .009). In a prevalent new-user cohort analysis, patients treated with tofacitinib had 68% reduced risk of ILD compared with adalimumab (aHR 0.32; 95% CI 0.13-0.82; P < .001). In an adjusted model, there was a 69% reduced risk of ILD in patients treated with tofacitinib compared with patients treated with adalimumab. Conclusions and Relevance: In this retrospective cohort of patients with RA, patients treated with tofacitinib had the lowest incidence of ILD compared with patients treated with all bDMARDs evaluated, and patients treated with tofacitinib had a reduced risk of ILD compared with patients treated with adalimumab after adjusting for important covariates. Additional prospective studies are needed to better understand the role tofacitinib may play in preventing ILD in patients with RA. These results, while significant, should be interpreted with caution given the fairly small sample size of the tofacitinib group.

Effects of Synbiotic Supplementation on Metabolic Syndrome Traits and Gut Microbial Profile among Overweight and Obese Hong Kong Chinese Individuals: A Randomized Trial.

In view of the limited evidence showing anti-obesity effects of synbiotics via modulation of the gut microbiota in humans, a randomized clinical trial was performed. Assessment of the metabolic syndrome traits and profiling of the fecal gut microbiota using 16S rRNA gene sequencing in overweight and obese Hong Kong Chinese individuals before and after dietary intervention with an 8-week increased consumption of fruits and vegetables and/or synbiotic supplementation was conducted. The selected synbiotic contained two probiotics (Lactobacillus acidophilus NCFM and Bifidobacterium lactis HN019) and a prebiotic (polydextrose). Fifty-five overweight or obese individuals were randomized and divided into a synbiotic group (SG; n = 19), a dietary intervention group (DG; n = 18), and a group receiving combined interventions (DSG; n = 18). DSG showed the greatest weight loss effects and number of significant differences in clinical parameters compared to its baseline values-notably, decreases in fasting glucose, insulin, HOMA-IR, and triglycerides and an increase in HDL-cholesterol. DSG lowered Megamonas abundance, which was positively associated with BMI, body fat mass, and trunk fat mass. The results suggested that increasing dietary fiber consumption from fruits and vegetables combined with synbiotic supplementation is more effective than either approach alone in tackling obesity.

Validation of a Deep Learning Algorithm for Continuous, Real-Time Detection of Atrial Fibrillation Using a Wrist-Worn Device in an Ambulatory Environment.

BACKGROUND: Wearable devices may be useful for identification, quantification and characterization, and management of atrial fibrillation (AF). To date, consumer wrist-worn devices for AF detection using photoplethysmography-based algorithms perform only periodic checks when the user is stationary and are US Food and Drug Administration cleared for prediagnostic uses without intended use for clinical decision-making. There is an unmet need for medical-grade diagnostic wrist-worn devices that provide long-term, continuous AF monitoring. METHODS AND RESULTS: We evaluated the performance of a wrist-worn device with lead-I ECG and continuous photoplethysmography (Verily Study Watch) and photoplethysmography-based convolutional neural network for AF detection and burden estimation in a prospective multicenter study that enrolled 117 patients with paroxysmal AF. A 14-day continuous ECG monitor (Zio XT) served as the reference device to evaluate algorithm sensitivity and specificity for detection of AF in 15-minute intervals. A total of 91 857 intervals were contributed by 111 subjects with evaluable reference and test data (18.3 h/d median watch wear time). The watch was 96.1% sensitive (95% CI, 92.7%-98.0%) and 98.1% specific (95% CI, 97.2%-99.1%) for interval-level AF detection. Photoplethysmography-derived AF burden estimation was highly correlated with the reference device burden (R2=0.986) with a mean difference of 0.8% (95% limits of agreement, -6.6% to 8.2%). CONCLUSIONS: Continuous monitoring using a photoplethysmography-based convolutional neural network incorporated in a wrist-worn device has clinical-grade performance for AF detection and burden estimation. These findings suggest that monitoring can be performed with wrist-worn wearables for diagnosis and clinical management of AF. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04546763.

Interactions of membrane active peptides with planar supported bilayers: an impedance spectroscopy study.

Membrane active peptides exert their biological effects by interacting directly with a cell's lipid bilayer membrane. These therapeutically promising peptides have demonstrated a variety of activities including antimicrobial, cytolytic, membrane translocating, and cell penetrating activities. Here, we use electrochemical impedance spectroscopy (EIS) on polymer-cushioned supported lipid bilayers constructed on single crystal silicon to study two pairs of closely related membrane active peptides selected from rationally designed, combinatorial libraries to have different activities in lipid bilayers: translocation, permeabilization, or no activity. Using EIS, we observed that binding of a membrane translocating peptide to the lipid bilayer resulted in a small decrease in membrane resistance followed by a recovery back to the original value. The recovery may be directly attributable to peptide translocation. A nontranslocating peptide did not decrease the resistance. The other pair, two membrane permeabilizing peptides, caused an exponential decrease of membrane resistance in a concentration-dependent manner. This permeabilization of the supported bilayer occurs at peptide to lipid ratios as much as 1000-fold lower than that needed to observe effects in vesicle leakage assays and gives new insights into the fundamental peptide-bilayer interactions involved in membrane permeabilization.

Cost Offsets of Treatment for Serious Mental Illness and Substance Use Disorder.

OBJECTIVE: The authors examined whether timely treatment for serious mental illness and substance use disorder reduces overall health care costs in a 3-year period. METHODS: Claims data from the IBM MarketScan Research Databases (2010-2017) were analyzed. The population studied included 2,997 Medicaid enrollees and 35,805 commercial insurance enrollees ages 18-64 years with an index event for a serious mental illness and 2,315 Medicaid enrollees and 28,419 commercial insurance enrollees with an index event for a substance use disorder. Health care costs in the 3 years after an index event were calculated for enrollees who received care that met a minimum threshold for treatment and for those who did not receive such care. The Toolkit for Weighting and Analysis of Nonequivalent Groups was used to control for statistically significant differences in pretreatment characteristics between the groups. RESULTS: All health care spending for enrollees who were engaged in behavioral health treatment for substance use disorder or a serious mental illness increased from year 0 to year 1 but decreased faster than the spending of enrollees who were not engaged in treatment, with larger trends for those engaged in substance use disorder treatment. Expenses for inpatient and emergency department care decreased over the 3 follow-up years; however, spending on outpatient services was significantly higher in all 3 follow-up years for those engaged in treatment. CONCLUSIONS: Health care delivery and payment models that improve access to behavioral health treatment may reduce emergency department, inpatient, and overall health care costs for particular subpopulations.

Adverse events among adult Medicaid enrollees with opioid use disorder and co-occurring substance use disorders.

BACKGROUND: It is common for adults with opioid use disorder (OUD) to misuse additional substances, and these individuals may be particularly at risk for adverse events, including mortality. Less is known about how continued receipt of prescription opioids or risk of adverse events (e.g., suicidality, overdose, poisoning) differs for people with co-occurring OUD and additional substance use disorders (SUDs). METHODS: We conducted a retrospective study using IBM® MarketScan® Multi-State Medicaid Database enrollment/claims data. We used logistic regression to measure the association between sample characteristics and our dependent variables. The sample consisted of non-Medicare-eligible adults aged 18-64 years who were continuously enrolled in Medicaid in 2016-2017 with an OUD diagnosis on at least one claim in 2016. RESULTS: Adults with OUD and a co-occurring SUD were more likely than adults with OUD only to have an opioid-related poisoning event (odds ratio [OR] = 1.488, p = .0052), all-cause poisoning (OR = 1.756, p < .0001), or suicidal ideation (OR = 1.796, p < .0001) but not to receive ongoing opioid prescriptions (OR = 0.973, p = .1626). Adverse events varied by OUD-SUD combination. For example, adults with OUD and cocaine use disorder had the highest odds of all-cause (OR = 2.393, p < .0001) or opioid-related (OR = 1.890, p = .0027) poisoning among those with a drug-specific diagnosis and were most likely to be diagnosed with suicidal ideation (OR = 2.465, p < .0001). CONCLUSIONS: This study provides evidence that adults with OUD and a co-occurring additional SUD have increased risk for several adverse events. Multisubstance use should be screened for and identified to determine the most appropriate course of treatment.

Chlorinated Spiroconjugated Fused Extended Aromatics for Multifunctional Organic Electronics.

The synthesis of a new molecule, SFIC-Cl, is reported, which features enhanced π-electron delocalization by spiroconjugation and narrowed bandgap by chlorination. SFIC-Cl is integrated into a single-crystal transistor (OFET) and organic light-emitting diode (OLED). The material demonstrates remarkable transport abilities across various solution-processed OFETs and retains efficient radiance in a near-infrared OLED emitting light at 700 nm. Furthermore, the intermolecular multi-dimensional connection of SFIC-Cl enables the fabrication of a single-component large-area (2 × 2 cm2 ) near-infrared OLED by spin-coating. The SFIC-Cl-acceptor-based solar cell shows excellent power conversion efficiency of 10.16% resulting from the broadened and strong absorption and well-matched energy levels. The study demonstrates that chlorinated spiroconjugated fused systems offer a novel direction toward the development of high-performance organic semiconductor materials for hybrid organic electronic devices.